Suppression of interleukin 2-dependent human T cell growth in vitro by prostaglandin E (PGE) and their precursor fatty acids. Evidence for a PGE-independent mechanism of inhibition by the fatty acids.
PGE represent oxygenation products of polyunsaturated essential fatty acids and are important regulators of cell-mediated immune responses. Because oils enriched in such fatty acids reduce inflammation and tissue injury in vivo, we examined the effects of these PGE precursors on IL-2-driven growth of human T lymphocytes. Dihomogamma linoleic acid (DGLA), AA, and their metabolites (PGE1 and PGE2, respectively) strongly inhibited short- and long-term growth of IL-2-dependent T cell cultures; EPA was much less inhibitory and its product, PGE3, failed to suppress IL-2 responses. Short-term pretreatment of the cells with DGLA or AA and removal of the fatty acids before the proliferation assay resulted in a smaller reduction in [3H]TdR incorporation. PGE and fatty acids did not alter the number of high affinity IL-2 binding sites on the T cell cultures but reduced the percentage of cells expressing CD25 and HLA class II molecules. No PGE was detected in supernatants from the fatty acid-treated cultures. Moreover, indomethacin, a cyclooxygenase inhibitor, did not reverse the antiproliferative effects of the fatty acids. Together, these findings indicate that fatty acids can inhibit IL-2-driven T cell growth via a PGE-independent mechanism and might be relevant to inflammatory diseases associated with persistent T cell activation.
Santoli
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Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104-4268.
Phillips
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Colt
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Zurier
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D015703:Antigens, CD / Q000032:analysis; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D011458:Prostaglandins E / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D015703:Antigens, CD; D005227:Fatty Acids; D007376:Interleukin-2; D011458:Prostaglandins E; D015375:Receptors, Interleukin-2